PROJECT SUMMARY/ABSTRACT Cochlear implants (CIs) have benefited more than 324,200 individuals worldwide who are deaf or severely hard of hearing since 1984. Although CIs can significantly improve auditory speech perception, leading to better quality of life for severe-to-profoundly deaf individuals, the success rate is highly variable and speech perception outcomes (SPOs) differ widely across CI users. Many factors can contribute to this wide variability, such as age of implantation, duration of deafness, level of preoperative usable residual hearing, pre-CI hearing aid use, and the design of CI electrodes. However, these factors explain only about 10-20% of the variance. Therefore, a large portion of the variance in post-surgical SPOs remains unclear and unpredictable, leading to great difficulty in determining who will benefit from a CI. The goal of this project is to identify the brain-based factors that determine the variability in SPOs in order to characterize the factors leading to successful SPOs. Functional magnetic resonance imaging (fMRI) and functional near-infrared spectroscopy (fNIRS) will be used to measure brain activity, and diffusion weighted imaging (DWI) will be used to measure white matter integrity prior to implantation; these measures will be contrasted with a group of normal hearing controls. After implantation, only fNIRS (which is fully compatible with a CI) will be used to measure changes in activity together with changes in speech perception at three- and six-month follow-up visits after the activation of the CI. The central hypothesis, formulated on the promising predictive powers of brain-based measures, is that pre-surgical neural markers predict SPOs following implantation. If this hypothesis is correct, pre-surgical brain imaging scans might be introduced in the evaluation process of CI candidacy. The long-term goal is to implement an imaging-guided process to determine pre-surgical CI candidacy and assist in post-surgical aural rehabilitation. The specific aims are to: 1) identify differences in activity and white matter integrity between adults with post-lingual sensorineural hearing loss (SNHL) and age- and gender-matched normal hearing controls; 2) determine neural markers that predict SPOs; and 3) identify changes in brain activity, specifically cross-modal reorganization in the post-lingual SNHL group, following implantation. By achieving these aims, the PI will gather data essential to developing a treatment protocol that involves brain imaging data to best guide clinical practices in adults and children, which will be proposed in a subsequent R01. Ultimately, the results of this research will reveal those neural factors important in predicting better SPOs in CI users and will lead to improved prognosis. The knowledge gained from this work will also shed light on opposing theoretical frameworks that account for the relationship between functional changes and SPOs in CI users. The foundational information established under this award will provide the framework for future research proposals aiming to collect imaging data in CI candidates for all ages in clinical practices. This study directly addresses Priority Areas 2 and 3 in Hearing and Balance Research of the latest NIDCD Strategic Plan.